Previous studies in our laboratory showed that continuous treatment of normal, human diploid cells with 2-20 nM concentrations of staurosporine (Stsp) induced reversible G1 arrest, while with the same treatment, transformed cells continued to cycle. Subsequent studies have shown that following brief treatment of cells with high levels of Stsp (150-200 nM), similar effects have been observed. The short-term treatment of cells did not significantly affect progression through S and G2/M phases of the cell cycle, but greater than 85% of the cells arrested in G and remained arrested for at least 96 h. Biochemical and FCM studies are being initiated to determine the effect of brief treatment on expression and functional activity cdk2, p53 and the G1 phase cyclins, D and E. It would appear from the initial studies that Stsp-sensitive phosphorylation events are operative in S and G2 phases that subsequently affect regulation through G1 phase.